tbuckley/cabot-search huggingface dataset:
A novel Bruton's tyrosine kinase inhibitor JDB175 shows potent efficacy to suppress central nervous system lymphoma
Authors: Yong Xia, Xue Li, Ning Jiang, Xiawei Wei
Journal: MedComm (2023)

Patients with central nervous system (CNS) lymphoma face limited treatment options and poor treatment outcomes, emphasizing the urgent need for effective therapeutic strategies. One limiting factor contributing to the suboptimal efficacy is the inadequate penetration of most treatment drugs across the blood-brain barrier (BBB). Recent insights into the pathophysiology of CNS lymphoma have identified the Bruton's tyrosine kinase (BTK) signaling pathway as a potential target. Some clinical trials have shown impressive responses to BTK inhibitors in CNS lymphoma. However, currently approved BTK inhibitors have low BBB penetration rates, limiting their efficacy. In this study, we discovered that JDB175, a novel and highly selective BTK inhibitor, exhibits excellent BBB penetration capabilities and demonstrates favorable activity in a mouse model of CNS lymphoma while showing no significant signs of toxicity. JDB175 effectively inhibits the BTK signaling pathway in human lymphoma cells, suppressing their proliferation, inducing cell cycle arrest, and promoting apoptosis. The significance of this study lies in addressing the critical unmet medical need for effective treatments for CNS lymphoma. This finding indicates a promising avenue for improved treatments in CNS lymphoma, potentially opening doors for further clinical investigation and therapeutic advancements.
Association between skin barrier development and early-onset atopic dermatitis: A longitudinal birth cohort study
Authors: John Chittock, Linda Kay, Kirsty Brown, Alison Cooke, Tina Lavender, Michael J. Cork, Simon G. Danby
Journal: Journal of Allergy and Clinical Immunology (2023)

A diagnosis of atopic dermatitis (AD) is common during infancy; however, it is unclear whether differential skin barrier development defines this period and signals disease onset in predisposed individuals.
Food insecurity and allergic diseases: A call to collective action
Authors: Stacie M. Jones, Sara Anvari, Amaziah Coleman, Robert D. Pesek, Kirsten M. Kloepfer, Tamara T. Perry, Akilah A. Jefferson, Dieu Doan, Aline Andres, Marcy Doderer, Ashlie Hilbun, Ryan Solomon, Amy M. Scurlock
Journal: Journal of Allergy and Clinical Immunology (2023)
The impact of vaccination and SARS-CoV-2 variants on the virological response to SARS-CoV-2 infections during the Alpha, Delta, and Omicron waves in England
Authors: Rachel Lunt, Catherine Quinot, Freja Kirsebom, Nick Andrews, Catriona Skarnes, Louise Letley, Donna Haskins, Catriona Angel, Skye Firminger, Kay Ratcliffe, Shelina Rajan, Angela Sherridan, Samreen Ijaz, Maria Zambon, Kevin Brown, Mary Ramsay, Jamie Lopez Bernal
Journal: Journal of Infection (2023)

Vaccination status and the SARS-CoV-2 variant individuals are infected with are known to independently impact viral dynamics; however, little is known about the interaction of these two factors and how this impacts viral dynamics. Here we investigated how monovalent vaccination modified the time course and viral load of infections from different variants. Regression analyses were used to investigate the impact of vaccination on cycle threshold values and disease severity, and interval-censored survival analyses were used to investigate the impact of vaccination on duration of positivity. A range of covariates were adjusted for as potential confounders and investigated for their own effects in exploratory analyses. All analyses were done combining all variants and stratified by variant. For those infected with Alpha or Delta, vaccinated individuals were more likely to report mild disease than moderate/severe disease and had significantly shorter duration of positivity and lower viral loads compared to unvaccinated individuals. Vaccination had no impact on self-reported disease severity, viral load, or duration if positivity for those infected with Omicron. Overall, individuals who were immunosuppressed and clinically extremely vulnerable had longer duration of positivity and higher viral loads. This study adds to the evidence base on disease dynamics following COVID-19, demonstrating that vaccination mitigates severity of disease, the amount of detectable virus within infected individuals and reduces the time individuals are positive for. However, these effects have been significantly attenuated since the emergence of Omicron. Therefore, our findings strengthen the argument for using modified or multivalent vaccines that target emerging variants.
Sulfated liposome-based artificial cell membrane glycocalyx nanodecoys for coronavirus inactivation by membrane fusion
Authors: Xu Li, Ningtao Cheng, Danrong Shi, Yutong Li, Chen Li, Miaojin Zhu, Qiao Jin, Zhigang Wu, Linwei Zhu, Yi He, Hangping Yao, Jian Ji
Journal: Bioactive Materials (2023)

As a broad-spectrum antiviral nanoparticle, the cell membrane nanodecoy is a promising strategy for preventing viral infections. However, most of the cell membrane nanodecoys can only catch virus and cannot induce inactivation, which may bring about a considerably high risk of re-infection owing to the possible viral escape from the nanodecoys. To tackle this challenge, sulfated liposomes are employed to mimic the cell membrane glycocalyx for constructing an artificial cell membrane glycocalyx nanodecoy that exhibits excellent anti-coronavirus activity against HCoV-OC43, wild-type SARS-CoV-2, Alpha and Delta variant SARS-CoV-2 pseudovirus. In addition, this nanodecoy, loaded with surface sulfate groups as SARS-CoV-2 receptor arrays, can enhance the antiviral capability to virus inactivation through destroying the virus membrane structure and transfer the spike protein to postfusion conformation. Integrating bio-inspired recognition and inactivation of viruses in a single supramolecular entity, the artificial cell membrane nanodecoy opens a new avenue for the development of theranostic antiviral nanosystems, whose mass production is favored due to the facile engineering of sulfated liposomes.
Prenatal and adult exposure to smoking and incidence of type 1 diabetes in children and adults – a nationwide cohort study with a family-based design
Authors: Yuxia Wei, Jessica Edstorp, Maria Feychting, Tomas Andersson, Sofia Carlsson
Journal: The Lancet Regional Health - Europe (2023)

Prenatal exposure to smoking is linked to a reduced risk of type 1 diabetes in children. We wanted to find out if the risk of adult-onset type 1 diabetes is reduced in individuals who are exposed to smoking prenatally or during adulthood.We linked Swedish, nationwide registers and prospectively analyzed incidence of type 1 diabetes in relation to maternal smoking during pregnancy and adult smoking. Everyone was followed until age 30 or year 2019. We employed cohort and sibling design and used adjusted Cox regression and conditional logistic regression.For analyses of maternal smoking there were 3,170,386 individuals (18,745 cases of type 1 diabetes) and for adult smoking 1,608,291 individuals (1274 cases). Prenatal exposure to smoking was associated with lower incidence of type 1 diabetes during childhood and young adulthood (age 20-24, Hazard ratio (HR) 0.76, 95% Confidence interval 0.67-0.87), but not at higher ages. The HR associated with adult smoking was estimated at 1.14 (CI 1.00-1.31) overall and 1.34 (CI 1.03-1.75) in those with family history of diabetes. In sibling analyses, the odds ratio (OR) of type 1 diabetes in relation to prenatal exposure was 0.71 (CI 0.62-0.81) in children and 1.06 (CI 0.75-1.51) in adults (age 19-30), while adult smoking conferred an OR of 1.59 (CI 1.08-2.35).These findings indicate that a reduced risk conferred by tobacco exposure is limited to the prenatal period and type 1 diabetes developing during childhood. Adult smoking may be a risk factor for adult-onset type 1 diabetes, especially in people with family history of diabetes.Swedish Research Councils, Swedish Diabetes and Novo Nordisk Foundations, China Scholarship Council.
Non-HDL cholesterol and residual risk of cardiovascular events in patients with ischemic heart disease and well-controlled LDL cholesterol: a cohort study
Authors: Malene Kærslund Hansen, Martin Bødtker Mortensen, Kevin Kris Warnakula Olesen, Pernille Gro Thrane, Michael Maeng
Journal: The Lancet Regional Health - Europe (2023)

Identifying patients at high residual risk of atherosclerotic cardiovascular disease (ASCVD) despite statin-treatment is of paramount clinical importance. We aim to investigate if non-high-density lipoprotein cholesterol (non-HDL-C) identifies residual risk of ASCVD and death in statin-treated patients with ischemic heart disease and low-density lipoprotein cholesterol (LDL-C) ≤ 1.8 mmol/L.Leveraging Danish regional and national registries, we identified statin-treated patients with ischemic heart disease who underwent coronary angiography (CAG) and attained LDL-C ≤ 1.8 mmol/L within a year post-CAG. Outcomes were myocardial infarction (MI), ASCVD (MI or ischemic stroke), and all-cause death occurring from one year after CAG to end of follow-up. Cox regression analyses obtained adjusted hazard ratios (HR).Between January 1, 2011, and December 31, 2020, we included 23,641 statin-treated patients with ischemic heart disease and LDL-C ≤ 1.8 mmol/L. During median follow-up of 4.1 years (IQR 2.4-6.1), 893 (3.8%) patients developed MI, 1207 (5.1%) ASCVD, and 3054 (12.9%) patients died. For ASCVD the adjusted HRs (95% confidence interval) for non-HDL-C < 25th percentile (<1.7 mmol/L) versus 25th-74th (1.7-2.1 mmol/L), 75th-94th (2.2-2.6 mmol/L), and ≥95th (≥2.7 mmol/L) percentile were 1.1 (0.9-1.3), 1.4 (1.1-1.7), and 1.8 (1.4-2.4), and for all-cause death 1.0 (0.9-1.1), 1.2 (1.1-1.4), and 1.4 (1.2-1.7), respectively.In a contemporary secondary prevention cohort of patients with well-managed LDL-C, non-HDL-C emerges as an easily accessible marker to detect patients facing high residual risk of ASCVD and death. These findings are important for preventive strategies extending beyond LDL-C targets.Research grant from the Novo Nordisk Foundation.
Epigenetic modification in liver fibrosis: Promising therapeutic direction with significant challenges ahead
Authors: Runping Liu, Yajing Li, Qi Zheng, Mingning Ding, Huiping Zhou, Xiaojiaoyang Li
Journal: Acta Pharmaceutica Sinica B (2023)

Liver fibrosis, characterized by scar tissue formation, can ultimately result in liver failure. It's a major cause of morbidity and mortality globally, often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases. However, current treatment options are limited, highlighting the urgent need for the development of new therapies. As a reversible regulatory mechanism, epigenetic modification is implicated in many biological processes, including liver fibrosis. Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases, although the current evidence is still controversial. This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications, including DNA methylation, histone modification, and RNA modification, in liver fibrotic diseases. The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted. Finally, available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed. In summary, elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.
Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis
Authors: Shuran Fan, Ming Qi, Qi Qi, Qun Miao, Lijuan Deng, Jinghua Pan, Shenghui Qiu, Jiashuai He, Maohua Huang, Xiaobo Li, Jie Huang, Jiapeng Lin, Wenyu Lyu, Weiqing Deng, Yingyin He, Xuesong Liu, Lvfen Gao, Dongmei Zhang, Wencai Ye, Minfeng Chen
Journal: Acta Pharmaceutica Sinica B (2023)

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAP
Development of Chinese herbal medicine for sensorineural hearing loss
Authors: Yunhao Wu, Jingwen Zhang, Qiuping Liu, Zhuang Miao, Renjie Chai, Wenyong Chen
Journal: Acta Pharmaceutica Sinica B (2023)

According to the World Health Organization's world report on hearing, nearly 2.5 billion people worldwide will suffer from hearing loss by 2050, which may contribute to a severe impact on individual life quality and national economies. Sensorineural hearing loss (SNHL) occurs commonly as a result of noise exposure, aging, and ototoxic drugs, and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear, which is mainly triggered by reactive oxygen species accumulation, inflammation, and mitochondrial dysfunction. Though recent advances have been made in understanding the ability of cochlear repair and regeneration, there are still no effective therapeutic drugs for SNHL. Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine. Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL, and elucidate their molecular mechanisms of action, to pave the way for further research and development of novel effective drugs in this field.
Awareness and Use of ChatGPT and Large Language Models: A Prospective Cross-sectional Global Survey in Urology
Authors: Michael Eppler, Conner Ganjavi, Lorenzo Storino Ramacciotti, Pietro Piazza, Severin Rodler, Enrico Checcucci, Juan Gomez Rivas, Karl F. Kowalewski, Ines Rivero Belenchón, Stefano Puliatti, Mark Taratkin, Alessandro Veccia, Loïc Baekelandt, Jeremy Y.-C. Teoh, Bhaskar K. Somani, Marcelo Wroclawski, Andre Abreu, Francesco Porpiglia, Inderbir S. Gill, Declan G. Murphy, David Canes, Giovanni E. Cacciamani
Journal: European Urology (2023)
Circulating tumor DNA landscape and prognostic impact of acquired resistance to targeted therapies in cancer patients: a national center for precision medicine (PRISM) study
Authors: Arnaud Bayle, Laila Belcaid, Lola-Jade Palmieri, Diego Teysonneau, Sophie Cousin, Mariella Spalato-Ceruso, Mihaela Aldea, Damien Vasseur, Melissa Alame, Laura Blouin, Isabelle Soubeyran, Claudio Nicotra, Maud Ngocamus, Antoine Hollebecque, Yohann Loriot, Benjamin Besse, Ludovic Lacroix, Etienne Rouleau, Fabrice Barlesi, Fabrice Andre, Antoine Italiano
Journal: Molecular Cancer (2023)

Abstract Background Despite the effectiveness of the various targeted therapies currently approved for solid tumors, acquired resistance remains a persistent problem that limits the ultimate effectiveness of these treatments. Polyclonal resistance to targeted therapy has been described in multiple solid tumors through high-throughput analysis of multiple tumor tissue samples from a single patient. However, biopsies at the time of acquired resistance to targeted agents may not always be feasible and may not capture the genetic heterogeneity that could exist within a patient. Methods We analyzed circulating tumor DNA (ctDNA) with a large next-generation sequencing panel to characterize the landscape of secondary resistance mechanisms in two independent prospective cohorts of patients (STING: n = 626; BIP: n = 437) with solid tumors who were treated with various types of targeted therapies: tyrosine kinase inhibitors, monoclonal antibodies and hormonal therapies. Results Emerging alterations involved in secondary resistance were observed in the plasma of up 34% of patients regardless of the type of targeted therapy. Alterations were polyclonal in up to 14% of patients. Emerging ctDNA alterations were associated with significantly shorter overall survival for patients with some tumor types. Conclusion This comprehensive landscape of genomic aberrations indicates that genetic alterations involved in secondary resistance to targeted therapy occur frequently and suggests that the detection of such alterations before disease progression may guide personalized treatment and improve patient outcome.
Magnesium-containing bioceramics stimulate exosomal miR-196a-5p secretion to promote senescent osteogenesis through targeting Hoxa7/MAPK signaling axis
Authors: Lei Qi, Xin Fang, Jinge Yan, Cancan Pan, Weiwen Ge, Jing Wang, Steve GF. Shen, Kaili Lin, Lei Zhang
Journal: Bioactive Materials (2023)

Stem cell senescence is characterized by progressive functional dysfunction and secretory phenotypic changes including decreased proliferation, dysfunction of osteogenic and angiogenic differentiation, increased secretion of the senescence-associated secretory phenotype (SASP), which bring difficulties for bone repair. Rescuing or delaying senescence of aged bone marrow mesenchymal stem cells (O-BMSCs) was considered as effective strategy for bone regeneration in aging microenvironment. Magnesium (Mg) ion released from bioceramics was reported to facilitate bone regeneration via enhancing osteogenesis and alleviating senescence. In this study, Akermanite biocreamics (Akt) containing Mg ion as a model was demonstrated to promote osteogenesis and angiogenesis effects of O-BMSCs by activating the MAPK signaling pathway in vitro. Moreover, the enhanced osteogenesis effects might be attributed to enhanced Mg-containing Akt-mediated exosomal miR-196a-5p cargo targeting Hoxa7 and activation of MAPK signaling pathway. Furthermore, the in vivo study confirmed that 3D-printed porous Mg-containing Akt scaffolds effectively increased bone regeneration in cranial defects of aged rats. The current results indicated that the exosomal-miR-196a-5p/Hoxa7/MAPK signaling axis might be the potential mechanism underlying Akt-mediated osteogenesis. The exosome-meditaed therapy stimulated by the released Mg ion contained in Akt biocreamics or other biomaterials might serve as a candidate strategy for bone repair in aged individuals.
Biomimetic “Gemini nanoimmunoregulators” orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages
Authors: Honglin Huang, Ningxi Li, Xiaodan Wei, Qingzhi Li, Junhan Guo, Geng Yang, Hong Yang, Lulu Cai, Yiyao Liu, Chunhui Wu
Journal: Acta Pharmaceutica Sinica B (2023)

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy. Here, a new type of spatiotemporal biomimetic "Gemini nanoimmunoregulators" was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death (ICD), tumor-associated macrophages (TAMs) phenotype reprogramming and programmed cell death ligand 1 (PD-L1) degradation. The "Gemini nanoimmunoregulators" PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine (mPDA) as nanovectors to deliver metformin (Met) and toll-like receptor 7/8 agonist resiquimod (R848) to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane (RM) inlaid with T7 or M2 peptides. mPDA/Met@RM-T7 (abbreviated as PM@RM-T7) was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity. Meanwhile, PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion. Subsequently, mPDA/R848@RM-M2 (abbreviated as PR@RM-M2) specifically recognized TAMs and reset the phenotype from M2 to M1 state, thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes. This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity, which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis. This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.
Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel
Authors: Hayder M. Al-kuraishy, Majid S. Jabir, Ali I. Al-Gareeb, Ali K. Albuhadily, Salim Albukhaty, Ghassan M. Sulaiman, Gaber El-Saber Batiha
Journal: Ageing Research Reviews (2023)
Mouse models of accelerated aging in musculoskeletal research for assessing frailty, sarcopenia, and osteoporosis – A review
Authors: Dilara Yılmaz, Neashan Mathavan, Esther Wehrle, Gisela A. Kuhn, Ralph Müller
Journal: Ageing Research Reviews (2023)

Musculoskeletal aging encompasses the decline in bone and muscle function, leading to conditions such as frailty, osteoporosis, and sarcopenia. Unraveling the underlying molecular mechanisms and developing effective treatments are crucial for improving the quality of life for those affected. In this context, accelerated aging models offer valuable insights into these conditions by displaying the hallmarks of human aging. Herein, this review focuses on relevant mouse models of musculoskeletal aging with particular emphasis on frailty, osteoporosis, and sarcopenia. Among the discussed models, PolgA mice in particular exhibit hallmarks of musculoskeletal aging, presenting early-onset frailty, as well as reduced bone and muscle mass that closely resemble human musculoskeletal aging. Ultimately, findings from these models hold promise for advancing interventions targeted at age-related musculoskeletal disorders, effectively addressing the challenges posed by musculoskeletal aging and associated conditions in humans.
A novel deep generative model for mRNA vaccine development: Designing 5′ UTRs with N1-methyl-pseudouridine modification
Authors: Xiaoshan Tang, Miaozhe Huo, Yuting Chen, Hai Huang, Shugang Qin, Jiaqi Luo, Zeyi Qin, Xin Jiang, Yongmei Liu, Xing Duan, Ruohan Wang, Lingxi Chen, Hao Li, Na Fan, Zhongshan He, Xi He, Bairong Shen, Shuai Cheng Li, Xiangrong Song
Journal: Acta Pharmaceutica Sinica B (2023)

Efficient translation mediated by the 5' untranslated region (5' UTR) is essential for the robust efficacy of mRNA vaccines. However, the
JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study
Authors: Marco Fischer, Peter Olbrich, Jérôme Hadjadj, Volker Aumann, Shahrzad Bakhtiar, Vincent Barlogis, Philipp von Bismarck, Markéta Bloomfield, Claire Booth, Emmeline P. Buddingh, Deniz Cagdas, Martin Castelle, Alice Y. Chan, Shanmuganathan Chandrakasan, Kritika Chetty, Pierre Cougoul, Etienne Crickx, Jasmeen Dara, Angela Deyà-Martínez, Susan Farmand, Renata Formankova, Andrew R. Gennery, Luis Ignacio Gonzalez-Granado, David Hagin, Leif Gunnar Hanitsch, Jana Hanzlikovà, Fabian Hauck, José Ivorra-Cortés, Kai Kisand, Ayca Kiykim, Julia Körholz, Timothy Ronan Leahy, Joris van Montfrans, Zohreh Nademi, Brigitte Nelken, Suhag Parikh, Silvi Plado, Jan Ramakers, Antje Redlich, Frédéric Rieux-Laucat, Jacques G. Rivière, Yulia Rodina, Pérsio Roxo Júnior, Sarah Salou, Catharina Schuetz, Anna Shcherbina, Mary A. Slatter, Fabien Touzot, Ekrem Unal, Arjan C. Lankester, Siobhan Burns, Mikko R.J. Seppänen, Olaf Neth, Michael H. Albert, Stephan Ehl, Bénédicte Neven, Carsten Speckmann
Journal: Journal of Allergy and Clinical Immunology (2023)